Apnoeic-Hypopnoeic Episodes During Obstructive Sleep Apnoea Are Associated With Histological Nonalcoholic Steatohepatitis

Poonam Mishra; Clarke Nugent; Arian Afendy; Chunhong Bai; Priya Bhatia; Mariam Afendy; Yun Fang; Hazem Elariny; Zachary Goodman; Zobair M. Younossi


Liver International. 2008;28(8):1080-1086. 

In This Article

Abstract and Introduction


Background: Nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnoea are associated with metabolic syndrome and atherosclerotic heart disease. This study evaluates the potential association between the NAFLD subtypes and a number of polysomnographical (PSG) parameters.
Methods: This study included patients undergoing bariatric surgery with extensive clinical and histological data for whom complete PSG data before surgery were also available. Excess alcohol intake and other causes of liver disease were excluded. Apnoea, hypopnoea and apnoea-hypopnoea index (AHI) were calculated as described previously.
Results: In this study, a total of 101 patients [77 nonalcoholic steatohepatitis (NASH) and 22 non-NASH controls] with PSG data were included (age 42.9 ± 11.4 years, body mass index 51.6 ± 9.5 kg/m2, fasting serum glucose 117.4 ± 53.4 mg/dl, fasting serum triglycerides 171.3 ± 82.9 mg/dl, 58% hypertension and 33% diabetes mellitus). Subjects with histological NASH had significantly lower lowest desaturation (77 vs. 85%, P=0.006), lower mean nocturnal oxygen saturation (91 vs. 93%, P=0.05), higher AHI (35 vs. 22, P=0.03), higher respiratory disturbance index (46 vs. 21, P=0.02) and higher alanine aminotransferase/aspartate aminotransferase ratio (1.4 vs. 1.3, P=0.05) compared with non-NASH controls. In multivariate analysis, the lowest desaturation (P=0.04) was independently associated with histological NASH. Lowest desaturation and mean nocturnal oxygen saturation were significantly lower in subjects with fibrosis (76 vs. 85%, P=0.004 and 90.4 vs. 93.0%, P=0.02).
Conclusions: Our results suggest that the frequent nocturnal hypoxic episodes in NAFLD patients may be a risk factor for developing NASH. Additional studies are needed to study the effect of optimizing sleep apnoea management on the outcomes of patients with NAFLD.


Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and is associated with obesity and insulin resistance.[1,2] Obstructive sleep apnoea (OSA) is also a very common condition, affecting up to 4% of adult males and 2% of adult females and up to 35% of obese individuals.[3,4,5] OSA is independently associated with insulin resistance.[6,7,8,9,10] Additionally, an association among sleep-disordered breathing, NAFLD and cardiovascular disease has been observed.[11,12,13,14,15] Recently, OSA has been reported as a new complication in cirrhotic patients with ascites.[16,17]

Theoretically, nocturnal hypoxaemic episodes during sleep apnoea may predispose patients to oxidative stress, which has been implicated in the pathogenesis of the progressive subtype of NAFLD. In fact, this oxidative stress has been suspected to play a key role in the development of nonalcoholic steatohepatitis (NASH) and its progression to advanced stages of hepatic fibrosis.[18]

In a previous study, an association between OSA and NAFLD was reported.[19] In the present study, we have used a different cohort of obese NAFLD patients with detailed histological, clinical and polysomnographical (PSG) data. Our aim was to further evaluate the association between these PSG parameters and different histological subtypes of NAFLD as well as hepatic fibrosis.


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